Hongqiao Hu, Li Zhang, Lei Cao, Jie Jiang, Yuqing Shi, Hong Guo, Yang Wang, Hai Li, Yan Zhang
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引用次数: 0
摘要
背景:人类呼吸道合胞病毒(HRSV人类呼吸道合胞病毒(HRSV)给婴儿和老年人带来了沉重的疾病负担。使用减毒活疫苗和某些载体疫苗对 HRSV 进行鼻内免疫接种已完成 II 期临床试验,安全性和有效性良好。I 型干扰素(IFN)作为一种天然粘膜佐剂,可显著增强抗原呈递细胞的处理和抗原呈递能力,促进 T 细胞和 B 细胞的产生。研究方法本研究采用人α2b干扰素(IFN-人)和小鼠α2干扰素(IFN-鼠)与融合蛋白(F)结合作为鼻腔粘膜佐剂。对 BALB/c 小鼠进行鼻内免疫,以评估制剂在体内的免疫原性。结果与 F 蛋白免疫组相比,F + IFN-Human 和 F + IFN-Mouse 实验组小鼠的中和抗体滴度显著升高,淋巴细胞分泌的 IFN-γ 和 IL-4 增加,且均能诱导小鼠产生高滴度特异性 IgA 抗体(p < 0.F+IFN-人免疫组诱导小鼠IgG和IgG1抗体滴度最高;但F+IFN-鼠免疫组诱导的中和抗体滴度最高(598),肺部病毒载量最低(Ct值为31),小鼠体重恢复最快。此外,F+IFN-小鼠免疫组小鼠的肺部病理损伤最轻(病理损伤总分为 2 分)。结论总之,IFN-小鼠作为HRSV重组蛋白疫苗的粘膜佐剂,与IFN-人佐剂相比,对小鼠的保护效果更佳。
Preliminary Study on Type I Interferon as a Mucosal Adjuvant for Human Respiratory Syncytial Virus F Protein.
Background: Human respiratory syncytial virus (HRSV) imposes a significant disease burden on infants and the elderly. Intranasal immunization using attenuated live vaccines and certain vector vaccines against HRSV has completed phase II clinical trials with good safety and efficacy.Recombinant protein vaccines for mucosal immunization require potent mucosal adjuvants. Type I interferon (IFN), as a natural mucosal adjuvant, significantly enhances antigen-presenting cell processing and antigen presentation, promoting the production of T and B cells. Methods: This study utilized human α2b interferon (IFN-human) and mouse α2 interferon (IFN-mouse) as nasal mucosal adjuvants in combination with fusion protein (F). Intranasal immunization was performed on BALB/c mice to evaluate the immunogenicity of the formulation in vivo. Results: Compared to the F protein immunization group, mice in the F + IFN-Human and F + IFN-Mouse experimental groups exhibited significantly increased neutralizing antibody titers and augmented secretion of IFN-γ and IL-4 by lymphocytes, and both of them could induce the production of high-titer specific IgA antibodies in mice (p < 0.001).The F + IFN-Human immunization induced the highest IgG and IgG1 antibody titers in mice; however, the F + IFN-Mouse immunization group elicited the highest neutralizing antibody titers (598), lowest viral loads in the lungs (Ct value of 31), and fastest weight recovery in mice. Moreover, mice in the F + IFN-Mouse immunization group displayed the mildest lung pathological damage (Total score of pathological injury was 2). Conclusions: In conclusion, IFN-Mouse, as a mucosal adjuvant for HRSV recombinant protein vaccines, demonstrated superior protective effects in mice compared to IFN-Human adjuvants.
VaccinesPharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
8.90
自引率
16.70%
发文量
1853
审稿时长
18.06 days
期刊介绍:
Vaccines (ISSN 2076-393X) is an international, peer-reviewed open access journal focused on laboratory and clinical vaccine research, utilization and immunization. Vaccines publishes high quality reviews, regular research papers, communications and case reports.